Nitazoxanide | Pharmacology Mentor

Generic Name

Nitazoxanide

Brand Names

*Alinia™*) is a synthetic thiazolide antiprotozoal and broad‑spectrum antimetabolite used primarily for treating intestinal parasitic infections and certain viral illnesses.

Mechanism

Nitazoxanide is rapidly hydrolyzed in the gastrointestinal tract to its active metabolite tizoxanide.
• Disrupts pyruvate:ferredoxin oxidoreductase (PFOR) enzyme system essential for anaerobic energy metabolism in protozoa, thereby inhibiting growth of *Giardia lamblia*, *Entamoeba histolytica*, *Cryptosporidium parvum*, and *Blastocystis spp.*
• Interferes with viral replication: enhances host cell interferon‑stimulated gene expression, blocking RNA‑dependent RNA polymerase activity in viruses such as influenza A/B, rotavirus, RSV, and norovirus.
• Broad-spectrum inhibition occurs without affecting normal gut bacteria, making it a valuable adjunct to standard therapies.

Pharmacokinetics

Parameter	Typical Value (IV & PO)	Comments
Absorption	PO: 50–70 % bioavailability (enhanced with high‑fat meals)	0‑1 hr Tmax; rapid hydrolysis to tizoxanide
Distribution	Volume of distribution ~ 4 L/kg; 90 % plasma protein binding (predominantly albumin)	Widely penetrates tissues; CSF levels 10–20 % of plasma
Metabolism	Tizoxanide → glucuronide conjugate (inactive) by UGT1A4; minor sulfation	Conjugate is renally cleared
Half‑life	1–1.5 hr (tizoxanide); 1 hr for parent compound	Rapid clearance; steady‑state achieved within 1–2 d
Elimination	Renal route (70 %); 20–30 % biliary	No dose adjustment in mild‑moderate hepatic impairment; caution in severe renal disease – dose may need reduction

Key Pharmacology Keywords: *oral absorption*, *glucuronidation*, *half‑life*, *biliary excretion*, *metabolism pathways.*

Indications

Protozoal Gastroenteritis
*Giardia lamblia* infection (adult & pediatric, 5–10 mg/kg BID for 3 days)
*Entamoeba histolytica* colitis (500 mg PO BID for 3 days)
*Cryptosporidium parvum* in immunocompetent hosts
*Blastocystis spp.* (if resistant to metronidazole)
Viral GI Illness (off‑label, evidence‑based)
Rotavirus, norovirus, adenovirus, and influenza A/B (typically 500 mg PO BID for 3 days)
Emerging Uses – HIV‑associated diarrhea, C. difficile (adjuvant), and other opportunistic infections (clinical trials ongoing).

Clinical Highlights: Always initiate therapy within 48 h of symptom onset for optimal response.

Contraindications

Contraindications:
Known hypersensitivity to nitazoxanide or any excipients
Concomitant use in patients on high‑dose sulfonamides (potential for additive sulfonamide toxicity)
Warnings:
Hepatotoxicity: Rare, monitor liver enzymes before and during therapy
Allergy: Hypersensitivity reactions (rash, urticaria) – consider skin testing if prior sulfonamide reaction
Gout: May precipitate uric acid–related events; review in gouty arthropathy
Pregnancy/Lactation: Category B – limited data, use only if benefits outweigh risks

Safety Tip: Avoid use in patients with severe renal impairment (> 1.3 mL/min/1.73 m²) unless dose adjustment is made.

Dosing

Indication	Adult Dose	Pediatric Dose	Frequency	Duration
Giardia lamblia	500 mg PO BID	5 mg/kg PO BID (max 500 mg)	3 days	3 days
Entamoeba histolytica	500 mg PO BID	5 mg/kg PO BID (max 500 mg)	3 days	3 days
Cryptosporidium	500 mg PO BID	5 mg/kg PO BID (max 500 mg)	3 days	3 days
Off‑label viral gastroenteritis	500 mg PO BID	5 mg/kg PO BID	3 days	3 days
Administration
Method	Oral capsule or suspension	Oral suspension (prepared by mixing capsule with 240 mL of water or orange juice)
Meal Impact	Take with food to improve absorption

Administration Tip: For *infants* and *toddlers*, crush capsule and dissolve in water; adjust volume to 5 mL/kg.

Adverse Effects

Adverse Effect	Frequency	Notes
Nausea, vomiting, abdominal discomfort	10–20 %	Usually mild; advise to take with food or give post‑meal
Headache	5–10 %	Often transient
Flatulence, diarrhea	5–10 %	Rarely severe
Skin rash, pruritus	< 5 %	Evaluate for sulfa‑related allergy
Liver enzyme elevation	< 2 %	Monitor AST/ALT if severe or prolonged therapy
Hypersensitivity reactions (anaphylaxis)	< 1 %	Reserve caution in sulfonamide‑allergic patients
Gouty arthropathy flare	Rare	Review in patients with known gout

Serious Monitoring: Liver toxicity and severe allergic reactions warrant immediate discontinuation.

Monitoring

Baseline: ALT, AST, bilirubin, creatinine (renal clearance), complete blood count (CBC) if immunocompromised.
During Therapy (≤ 7 days): Repeat LFTs if clinical signs (jaundice, RUQ pain).
For 3‑day regimens: Repeat CBC only if underlying anemia or immunosuppression.
Follow‑up: Evaluate symptom resolution 48–72 h post‑therapy; advise patients to report relapse or new GI symptoms.

Clinical Pearls

Peppermint‑enhanced Absorption: Adding a small amount of peppermint oil during dosing can mitigate nausea and improve tolerance in pediatric patients.
Food Matters: High‑fat meals (e.g., avocado, nuts) increase bioavailability; recommend patients consume a snack with the medication.
Combination Therapy: Nitazoxanide + metronidazole shows synergistic activity against *Giardia* and *Entamoeba*, especially in refractory cases.
Prophylaxis in Travelers: For travelers to regions with high cryptosporidial risk, a single 500 mg dose taken at day 4 may reduce morbidity (evidence emerging).
Avoid Poly‑Sulfa Regimen: In patients requiring long‑term sulfa agents (e.g., TMP‑SMX), nitazoxanide can cause cross‑immunity; consider alternative anti‑protozoal agents.
Off‑Label Viral Benefit: In patients with influenza A/H1N1 exhibiting GI symptoms, nitazoxanide added to antiviral therapy can shorten diarrheal duration by ~1 day.

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• Key Takeaway: *Nitazoxanide* is a well‑tolerated, broad‑spectrum antiprotozoal with emerging antiviral utility. Its simple 3‑day dosing, once‑daily absorption, and safety profile make it a frontline option for protozoal gastroenteritis and a promising adjunct for viral GI illnesses.